pN1 Disease Research Articles

Trends and Predictors of Adjuvant Therapy for Adverse Features Following Radical Prostatectomy: An Analysis From Cancer of the Prostate Strategic Urologic Research Endeavor

OBJECTIVETo determine trends and predictors of adjuvant therapy in patients with adverse features at radical prostatectomy (RP), and to investigate the associations of adjuvant therapy and adverse feature type with survival. METHODSFrom the Cancer of the Prostate Strategic Urologic Research Endeavor registry (1990-2017), 2209 men with adverse features (pT3N0M0 disease and/or positive surgical margins), and 108 men with positive lymph nodes (pN1) at RP were identified. Temporal trends were evaluated, and predictors of adjuvant therapy were assessed with multivariate logistic regression. Kaplan-Meier analysis and competing risks regression were used to test cumulative incidence and risk of all-cause and prostate cancer-specific mortality. RESULTSOf 2209 men with adverse features and pN0 disease, 89 (4.0%), 82 (3.7%), and 30 (1.4%) received adjuvant external beam radiation therapy (ERBT) alone, androgen deprivation therapy (ADT) alone, or combined EBRT and ADT, respectively. Of 108 men with pN1 disease, 54 (50%) received ADT with or without EBRT. Adjuvant treatment for patients with adverse features decreased from 13.3% (1990-1994) to 6% or less (2005-2017, Ptrend <.001). Patients with margin positive pT3a (odds ratio 4.13; 95% confidence interval 2.21-7.73; P<.01) and margin positive pT3b disease (odds ratio 7.09; 95% confidence interval 3.66-1.73; P<.01) had greater odds of receiving adjuvant therapy compared to patients with margin negative pT3a disease. Adverse feature type was associated with prostate cancer-specific mortality in univariate analysis (log-rank P <.01), but not in competing risks regression (P= .06). CONCLUSIONAdjuvant therapy declined for men with adverse features at RP. Providers do not treat all adverse feature types the same way, despite broad treatment recommendations in guidelines.

Prognostic Impact of the Number of Metastatic Lymph Nodes on the Eighth Edition of the TNM Classification of NSCLC

IntroductionCurrent nodal staging of NSCLC is defined only by anatomical location of lymph nodes (LNs). The aim of this study is to investigate prognostic impacts of the number of metastatic LNs by stratifying the present N classification. MethodsWe analyzed 1989 patients with NSCLC who underwent complete resection by lobectomy or pneumonectomy involving dissection of the hilar and mediastinal LNs from 2003 to 2012. We classified patients according to the number of metastatic nodes and stations and their current category of metastatic LNs. We analyzed the overall survival in each group and assessed the survival impact of the combination of them. ResultsIn the multivariate analyses of all patients, pathological N1 (pN1) (reference [ref.] pN2) and single-node metastasis (ref. multiple-node) were independent prognostic factors whereas single-station metastasis (ref. multiple-station) was not. In the respective multivariate analyses of pN1 and pN2 disease, multiple-node metastasis (ref. single-node) was an independent prognostic factor in pN1 disease (hazard ratio: 1.41, p = 0.04), but not in pN2 disease. Investigation for other boundaries of a number of metastatic LNs of three or more (ref. one to two), four or more (ref. one to three), and five or more (ref. one to four) found that all of them were independent prognostic factors in both pN1 and pN2 diseases. ConclusionsThe number of metastatic LNs had a strong impact on survival in addition to the current pN classification. To clarify its prognostic impact, further study is needed in other datasets including patients treated by nonsurgical modalities.

Metabolic tumor volume of metastatic lymph nodes and survival after total laryngectomy in laryngeal and hypopharyngeal cancer

ObjectivesThe prognostic value of metabolic tumor volume (MTV) in locally advanced laryngeal or hypopharyngeal cancer is established in the setting of chemoradiotherapy, while it remains unknown in the setting of upfront total laryngectomy. Materials and methodsWe retrospectively analyzed 88 patients receiving total laryngectomy and neck dissection, using Cox regression models. Results and conclusionVariables related to metastatic lymph node were associated with overall survival, whereas those related to primary tumor were not. In multivariable models, MTV of metastatic lymph nodes (N-MTV) as a continuous variable (Akaike’s information criterion (AIC), 277.5) was equivalent to pathological nodal status (AIC, 278.2; P = 0.40), and superior to pathological nodal classification as an ordinal variable (AIC, 281.4; P < 0.05) in ability of predicting death. The risk of death was increased by 1.2-fold (95% confidence interval (CI), 1.0–1.4; P = 0.03) every 10-ml increment of N-MTV, while patients with pN+ disease were at a higher risk of death by 2.9-fold (95% CI, 1.0–12.2; P < 0.05) compared with patients with pN0 disease. Using recursive partitioning analysis (RPA), we classified the patients as having a low, intermediate, or high risk of death on the basis of N-MTV and extranodal extension (ENE). This RPA classification system exhibited greater concordance with overall survival than the classification considering pathological nodal status and ENE (AIC, 275.8 versus 281.4; P = 0.02). In the setting of upfront total laryngectomy, N-MTV is a critical predictor of mortality. A staging system in which N-MTV is incorporated may better inform adjuvant treatment decisions.

Outcomes of neoadjuvant chemotherapy using gemcitabine and cisplatin in muscle invasive bladder cancer: A retrospective analysis of the patient and treatment factors in a single institute.

Meta-analysis had shown a significant 5% absolute survival benefit in favour of neoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy before radical cystectomy (RC) and pelvic lymphadenectomy (PLND) for patients with muscle invasive bladder cancer (MIBC). Those who had pathological complete response (pCR) to NAC could have long-term progression-free survival (PFS) and overall survival (OS). To identify the treatment and patient factors which could predict a pCR to NAC and the associated PFS and OS in a single institute. We retrospectively reviewed the records of patients who had received NAC with gemcitabine and cisplatin (GC) in our centre from January 2004 to December 2017. The patients' age, tumour stage, baseline estimated glomerular filtration rate (eGFR), chemotherapy chart, and pathological information were recorded. There were 25 men and five women who had received NAC followed by RC. pCR was noted in the surgical specimen of 11 (37%) patients. The mean dose of gemcitabine was significantly higher in the pCR group than the non-pCR group (9850 vs 7852mg, P=0.039) as was the dose-intensity of cisplatin (87.4% vs 71.3%, P=0.044). After a median follow-up of 38months (range 4.3-154), seven patients had disease progression. The estimated 3-year PFS is 74.9% (95% confidence interval [CI], 66.7%-83.3%). None of the patients who achieved pCR relapsed, while six out of seven patients who had pN1 disease developed distant metastasis (DM). Only two patients died of DM while two other patients died of unrelated causes. The estimated 3-year OS is 88.9% (95% CI 82.8%-95%). We have demonstrated that the dose intensity of GC is a major determinant of pCR, which predicts longer RFS and OS. Further research in gene expression profiling of MIBC to help selecting patient for NAC is needed.

Lymph node metastasis outside of a tumor-bearing lobe in primary lung cancer and the status of interlobar fissures: The necessity for removing lymph nodes from an adjacent lobe.

The new Tumor Node Metastasis staging system does not recognize fissure status with respect to adjacent lobe invasion (ALI) in lung cancer. Furthermore, no specific surgical strategies have been recommended for lymph node dissections around adjacent nontumor-bearing lobes (NTBLs) according to fissure status. Therefore, this study was undertaken to investigate the necessity of removing additional adjacent lobe lymph nodes in patients with nonsmall cell lung cancer (NSCLC) for lesions limited to in the vicinity of the interlobar fissure.From August 2013 to March 2015, the records of 332 patients, who underwent systematic mediastinal lymph node dissection, were reviewed in this retrospective study. The bronchial lymph nodes had been subjected to pathological examination, and the status of the fissures was also recorded. A statistical analysis was performed to identify the significant predictors of lymph node metastasis.The patients were divided into a nonadjacent lobe invasion (NALI) group (n = 295) and an ALI group (n = 37). There was a significant difference in tumors with pN2 disease between the ALI and NALI groups (37.8% vs 8.8%, P = .001). ALI tumors had significantly more frequent pleural involvement than NALI tumors (62.2% vs 43.1%, P = .035). The frequency of N2 involvement among tumors invading across the complete fissure was higher than that of the tumors invading across the incomplete fissure (44.4% vs 14.3%, P = .015). However, the frequency of N1 involvement among tumors invading across the incomplete fissure was not statistically different than that of tumors not invading across incomplete fissure (32.1% vs 24.2%, P = .357). Regarding lymph node metastasis in NTBL, 15 (12.7%) patients had lymph node metastases in NTBLs. Pleural involvement was an independent predictor of lymph node metastasis in an NTBL.A greater frequency of N2 lymph nodes existed in NSCLC with invading adjacent lobe across complete fissure, extensive lymphatic resection within the hilum, and NTBL in tumors with pleural involvement are justifiable and necessary.

Fumarate hydratase expression in localized, radically-resected clear cell renal cell carcinoma and its association with clinical outcomes.

620 Background: Prognostic stratification of localized clear cell renal cell carcinoma (lccRCC) mainly relies on clinical characteristics and TNM staging system, while biological biomarkers are currently lacking. We previously showed that reduced expression of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) was associated with better clinical outcomes in patients (pts) with metastatic ccRCC. In the present study we aimed at assessing the association between intratumor FH expression and clinical outcomes in pts with radically-resected lccRCC. Methods: Pts with radically-resected lccRCC and available formalin-fixed, paraffin-embedded (FFPE) primary (renal) tumor tissue were included. FH protein expression was assessed by means of immunohistochemistry (IHC) and defined as normal (comparably to non-neoplastic tubular cells) or low (lower than in non-neoplastic tubular cells). Results: Out of 50 pts included, we found a normal FH expression in 20 cases (40%) and a low FH expression in 30 cases (60%). Median age was 57 years (interquartile range 49-68) and 48 pts (96%) had pN0 disease, while 2 pts (4%) had pN1 disease. Low FH expression was associated with pT ( P= .003) but not with sex, age, Fuhrman grade or pN. After a median follow-up of 76.9 months, low FH expression was associated with a lower relapse rate (13% vs 50%; odds ratio for relapse 0.16; 95% confidence interval [CI] 0.04-0.62; P= .005), longer relapse-free survival (RFS) (5-years RFS rate 90% vs 50%; HR 0.20; 95% CI 0.06-0.63; P= .006) and a trend toward a better overall survival (OS) (5-years OS rate 100% vs 77.3%; HR 0.14; 95% CI 0.02-1.23; P= .07) when compared with normal FH expression. In the multivariable model including other characteristics associated with RFS, low FH expression confirmed an independent association with RFS (adjusted HR 0.25; 95% CI 0.06-0.91; P= .03). Conclusions: In our study, low intratumor FH, as detected by IHC, was associated with lower relapse rate, better RFS and a trend toward a better OS in patients with lccRCC when compared with normal FH levels. The role of FH expression as a prognostic biomarker in this setting warrants further investigation.

Evaluating the clinical, environmental, genetic, and genomic profile of men with early-onset aggressive prostate cancer (PCa).

TPS333 Background: Although PCa incidence has stabilized or decreased in most age groups, the incidence of metastatic disease has increased among men 50-69 years old. The incidence of fatal PCa has decreased for most age groups, it has remained unchanged in men under 55 years old. These observations are supported by data from 3 randomized trials. In S9346 in newly diagnosed M1, 18% of men (all-comers N = 3040) were ≤ 60 years. A significant percentage of younger men enrolled in CHAARTED had de-novo metastases at diagnosis; among 575 patients without prior local therapy, the median age was 62 years, and among men &lt; 60 years old (n = 274), 80.3% (n = 220) had de novo metastatic disease. Lastly, in S9921 (N = 983) 15% of men ≤ 60 years had pN1 disease at enrollment. A significant proportion of men with metastatic disease progress to castration -resistance within a short interval of initiating androgen-deprivation therapy (ADT) ± docetaxel or abiraterone for metastatic hormone sensitive PCa. Pivotal studies have described genetic abnormalities in aggressive localized or end stage prostate cancers, but early-onset cases and those with early progression on systemic therapy are not included or are under-represented in these studies. Methods: The primary objective of this multi-institutional trial is to characterize the clinical, environmental, genetic and genomic features of high-risk advanced PCa: Cohort 1: men ≤ 60 years old with N1 or M1 at diagnosis or who develop metastases shortly after local therapy; Cohort 2: men with early progression to castration-resistant PCa in ≤ 1 year on ADT ± docetaxel or ADT ± abiraterone. Clinical and environmental history, peripheral blood for cell free DNA and germline analysis will be collected. Primary/metastatic tumor tissue will be tested via the Tempus platform, which includes DNA sequencing, whole transcriptome expression profiling, copy number analysis, comprehensive fusion gene analysis and calculation of tumor mutational burden. We will also prospectively correlate clinical and molecular characteristics with outcomes. To date, 5 patients have been registered.

Development of a liquid-biopsy-based technique for the supplementary diagnosis of highly advanced lymph node metastasis in patients with locally advanced gastric cancer.

56 Background: The outcomes of patients with locally advanced gastric cancer who have highly advanced lymph node metastasis such as N3 remain poor despite radical resection. If the preoperative diagnoses of such patients improve, further improvement in treatment outcomes is expected to be obtained by means of personalized therapies such as preoperative chemotherapy; however, the accuracy of diagnosis remains unsatisfactory. Therefore, exploratory proteome analysis using sera was performed with the aim of developing a supplementary liquid-biopsy-based technique to diagnose highly advanced lymph node metastasis in patients with locally advanced gastric cancer. We report the results obtained thus far. Methods: The subjects were 24 patients with pT4a gastric cancer (12 with pN0 disease and 12 with pN3 disease). Proteins that had significantly different (P&lt;0.001) expression levels in the preoperative serum on exploratory proteome analysis by liquid chromatography and mass spectrometry were identified. These proteins were verified by Enzyme-Linked ImmunoSorbent Assay (ELISA) using a different cohort (20 patients with pN0 disease and 13 with pN3 disease) from that described above. Results: In the exploratory proteome analysis, 2,357 kinds of proteins were identified and examined. Six these proteins were identified as candidate predictive markers of highly advanced lymph node metastasis. These proteins were verified using existing and newly developed ELISA kits, and reproducibility was verified for one protein (Protein V) (P = 0.003). Conclusions: The possibility of the supplementary diagnosis of highly advanced lymph node metastasis by liquid biopsy was suggested in patients with locally advanced gastric cancer. Further evaluations by prospective studies are now in progress, with the ultimate goal of clinical application.

The Prognosis Value of Lymphatic Vessel Invasion in pN0 Gastric Cancer Patients with Insufficient Examined Lymph Nodes

ObjectivesTo investigate the prognosis value of lymphatic vessel invasion (LVI) in pN0 gastric cancer patients with insufficient examined lymph nodes (ELNs). MethodsClinicopathologic and prognostic data of pN0 gastric cancer patients with insufficient ELNs who underwent radical surgery in our institution were retrospectively studied. ResultsFirstly, we confirmed that less than 16 but not less than 30 ELNs were insufficient ELNs in the present study. Of the 350 pN0 patients with < 16 ELNs, 64 patients (18.29%) had LVI. The overall survival (OS) of patients with LVI was significantly poorer than those without LVI. Multivariate analysis suggested that LVI was one of the independent factors predicting prognosis of pN0 patients with < 16 ELNs. Further analyses suggested that there were similar prognoses between pN0 patients with < 16 ELNs who had LVI and pN1 patients, and between pN0 patients with < 16 ELNs who had no LVI and pN0 patients with ≥ 16 ELNs, respectively. Therefore, we proposed a novel pN classification, in which LVI-positive pN0 gastric cancer with < 16 ELNs was classified as pN1 disease. Two-step multivariate analysis demonstrated that the novel pN classification was more suitable for prognostic assessment than the original one. ConclusionsLVI is a powerful and independent prognostic factor for pN0 gastric cancer patients with < 16 ELNs, and node-negative gastric cancer with < 16 ELNs which had LVI should be considered as node-positive disease. LVI is an effective indicator identifying patients stage migration happens to in pN0 patients with < 16 ELNs.

Positive impact of the negative lymph node count on the survival rate of stage III colon cancer with pN1 and right-side disease.

Background: We aimed to investigate the role of the negative lymph node count (NLN) as a predictor of prognosis in patients with stage III colon cancer.Methods: We conducted a retrospective study on patients who were diagnosed with stage III colon cancer at Sun Yat-sen University Cancer Center. According to the number of negative lymph nodes, all patients were divided into the low or high NLN group. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and log-rank test between the two groups. Univariate and multivariate Cox proportional hazards models were used to evaluate the risk factors for survival.Results: The time-dependent receiver operating characteristic (ROC) curve showed that the optimal cutoff value of NLN was nine. In total, 167 and 298 patients were distributed into the low and high NLN groups, respectively. Patients in the high NLN group tended to present with a greater proportion of right-side colon cancer and pN1 stage disease, superior DFS (P < 0.001) and OS (P = 0.001) than those in the low NLN group. Multivariable analyses confirmed increased NLN as a positive prognostic variable, independent of other potential confounding factors. Subgroup analysis showed that in patients with a right-side location, those with 9 or fewer negative lymph nodes had a 5-year OS rate of 35.4% versus 77.1% in those with more than 9 negative lymph nodes evaluated (P < 0.001). For patients with stage pN1, those with NLN ≤9 exhibited an inferior 5-year OS rate than those with NLN > 9 (71.1% vs 84.8%, respectively; P = 0.009). There was no association between the number of negative lymph nodes identified and survival for patients with stage pN2 and left-side disease.Conclusion: NLN is an important prognostic factor for stage III colon cancer patients with right-side and stage pN1 disease other than for patients with stage pN2 and left-side disease, which can be partly explained in terms of inflammation and immunity.

Benefits of Elective Para-Aortic Radiotherapy for pN1 Prostate Cancer Using Arc Therapy (Intensity-Modulated or Volumetric Modulated Arc Therapy): Protocol for a Nonrandomized Phase II Trial.

BackgroundIn patients with prostate cancer (PCa) with histopathologically proven pelvic lymph node (LN) metastasis (pN1) after extended pelvic lymph node dissection (ePLND), multimodality treatment consisting of treatment of the primary tumor and whole pelvic radiotherapy (WPRT) combined with androgen deprivation therapy (ADT) offers promising results, leading to better cause-specific survival rates compared with ADT alone. However, in case more than one pelvic LN is invaded by the tumor, approximately 40% of the patients relapse biochemically and clinically. Clinical relapse is present in the para-aortic LNs (M1a disease) in up to 77% of the relapsing cases.ObjectiveWe hypothesize that, based on the evidence that positive LNs represent the door to hematogenous dissemination, elective para-aortic irradiation will reduce the development of both retroperitoneal nodal (M1a) and distant metastasis (M1b or M1c disease), postpone the need for palliative ADT, and prolong the time to castration-refractory disease.MethodsTo test this hypothesis, we will conduct a prospective, nonrandomized phase II trial to study the efficacy of additional elective para-aortic radiotherapy (PART) in pN1 patients compared with those who were historically treated with adjuvant WPRT alone. We aim to include 137 patients with PCa and presence of pN1 disease after ePLND. With this number of patients, an improvement of 15% in the 5-year clinical relapse-free survival can be detected with a power of 80%.ResultsRecruitment of patients for this trial started in 2017 and will be completed approximately by March 2020.ConclusionsThis is the first phase II trial to investigate the benefits of an elective PART in patients with PCa. The results of this trial will potentially serve as a sound base for a later randomized phase III trial. All participants are given a PART information sheet and required to give written informed consent. Results are expected to be published in a peer-reviewed journal.Trial RegistrationClinicalTrials.gov NCT03079323; https://clinicaltrials.gov/ct2/show/NCT03079323 (Archived by WebCite at http://www.webcitation.org/73ELimv1d)International Registered Report Identifier (IRRID)PRR1-10.2196/11256

How many lymph nodes are enough?-defining the extent of lymph node dissection in stage I-III gastric cancer using the National Cancer Database.

Surgical resection with lymph node dissection is the primary therapeutic modality for gastric cancer. National Cancer Database (NCDB) was used to determine the extent of lymph nodes (LNs) dissection for gastric cancer. The NCDB was queried from 2004-2013 for patients with margin-negative, invasive resected gastric cancer. The optimal number of LNs dissected was determined using a univariate χ2 cut-point analysis. Multiple sensitivity analyses were utilized to decrease bias. A total of 17,851 patients were included. For all patients, the optimal number of LNs needed to be examined was 20+ nodes. When correcting for stage migration (<7 LNs removed), the optimal cut-off value was 20+ LNs. When stratifying by pathologic nodal stage, the cut-off point was 10+ LNs for pN1 and pN2. The 5-year survival was 30.6%±1.6% for 0-9 removed LNs compared to 48.2%±1.2% for 10+ removed LNs (P<0.001) in pN1 disease and 18.3%±1.7% for 0-9 removed LNs compared to 32.6%±1.2% for 10+ removed LNs (P<0.001) in pN2 disease. For pN3 disease, the optimal cut-off point was 20+ LNs; the 5-year survival was 17.2%±1.3% for 0-19 removed LNs compared to 28.5%±1.7% for 20+ removed LNs (P<0.001). Moreover, the outcome was inferior among patients who had >10% positive dissected LNs (P<0.05). The extent of dissected lymph nodes of 20 or greater lymph nodes was associated with superior survival. Extended LN dissection is to be considered especially in patients with clinical lymphadenopathy.

Upfront surgery in patients with clinical skip N2 lung cancer based on results of modern radiological examinations.

Direct lymphatic drainage from a primary tumor to the right paratracheal or aortic window lymph nodes is often noted in pN2 disease. This multi-institutional retrospective study investigated the outcomes of upfront surgery in patients with clinical skip N2 disease (N2 disease without N1 disease) and a tumor in the right upper lobe or left upper segment based on results of modern radiological examinations, including positron emission tomography (PET). We identified 143 patients with cN2 disease who underwent upfront surgery in 12 institutions under the Thoracic Surgery Study Group of Osaka University between January 2006 and December 2013. Among 143 patients, 94 who underwent PET were analyzed. We classified these patients into Group A (n=39; clinical skip N2 disease and a tumor in the right upper lobe or left upper segment) and Group B (n=55; other). The median follow-up was 56.5 months. Among the 94 patients, 50 (53.2%) had skip N2 disease and 65 (69.1%) had a tumor in the right upper lobe or left upper segment. The 5-year overall survival (OS) rates of the 94 patients with cN2 disease was 47.9%. The 5-year OS rates for the cN2pN0/1 (n=22) and cN2pN2 (n=70) groups were 74.9% and 41.2%, respectively (P=0.034). The univariate analysis of OS revealed no significant differences in age, sex, histology, carcinoembryonic antigen (CEA) level, tumor size, PET findings, and number of metastatic lymph nodes when these parameters were dichotomized. A significantly better 5-year OS rate was observed in Group A than in Group B (64.0% vs. 37.0%; P=0.039). The multivariate analysis of OS revealed that Group A was a significantly prognostic factor (P=0.030). Patients with cN2 disease in Group A had a more favorable prognosis. Upfront surgery may be a treatment option for such selected patients with non-small lung cancer in the specific group.

Association of adjuvant radioactive iodine therapy with survival in node-positive papillary thyroid cancer

PurposeTo assess the effect of adding radioactive iodine (RAI) therapy to total thyroidectomy (TT) on overall survival (OS) in patients presenting with papillary thyroid cancer (PTC) and cervical pathologically proven LN metastases (pN1). Methods and materialsWe identified a cohort of patients with PTC and nodal metastases treated with TT alone or TT plus RAI in the Surveillance, Epidemiology and End Results database between 2004 and 2013. Propensity score 1-to-1 matching was used to balance baseline characteristics. Cox proportional hazards regression models and Kaplan-Meier survival analysis were used to test the relationship between RAI and OS. ResultsIn all, 15,953 patients were identified. After propensity score matching, 12,128 patients remained in each group. Based on multivariate Cox analysis, patients treated with TT + RAI had a statistically significant improvement in OS compared with those treated with TT alone [hazard ratio (HR) = 0.54, P < 0.001)], and significance persisted in the matched cohort (HR = 0.41, P < 0.001). In a subgroup analysis, the survival benefit was observed among patients ≥55 years but not among those <55 years (age < 55: HR = 1.06, P = 0.72; age ≥ 55: HR = 0.33, P < 0.001). Patients with stage T4 benefited most from RAI treatment (HR = 0.29, P < 0.001). ConclusionThis propensity-matched analysis suggests that RAI therapy after TT was associated with improved OS in PTC patients with pN1 disease. Adjuvant RAI therapy needs to be considered in this patient group.

Increasing use of Hypofractionated Whole Breast Irradiation: An Analysis of Practice Patterns within a State-Wide Quality Consortium

Randomized clinical trials support the efficacy and safety of hypofractionated whole breast irradiation (H -WBI) in select patients with early stage breast cancer following breast conserving surgery. Existing 2011 ASTRO consensus guidelines suggest appropriateness criteria for the use of H -WBI based on subsets of patients well represented in these trials, including patients ≥50 years of age, pT1-2/pN0 disease, patients who did not receive systemic chemotherapy, and radiation treatment plans with dose heterogeneity within ∼7%. This longitudinal study reports the use of H-WBI in patients treated in practices collaborating in a state-wide quality consortium. We identified women in the consortium database who received whole breast irradiation between the years 2012 (11 participating institutions, 638 cases) and 2017 (22 institutions, 1295 cases). We determined the proportion of H-WBI cases (as a percentage ±95% CI) over time within various patient subgroups that satisfied all or some guideline criteria. We used separation (SEP) >25 cm along the central axis as a surrogate for dose heterogeneity. The most common H-WBI regimens utilized were 42.56 Gy/16 fractions (80% of cases) and 40 Gy/15 fractions (10% of cases). A boost of 10-10.64 Gy/4 fractions (51%), 10 Gy/5 fractions (31%), or 12 Gy/6 fractions (8%) was delivered to the surgical cavity in 88% (2012) and 81% (2017) of all cases. In the consortium as a whole, the use of H-WBI increased from 22%±3% to 61%±3% from 2012 to 2017. Among patients who met all consensus criteria, H-WBI use increased from 86%±14% to 99%±2% for patients who did not receive a boost and from 22%±7% to 85%±5% for those who received a boost. Similar increases in H-WBI use were observed independent of histology (IDC vs. ILC), receptor status (ER positive vs. ER negative vs. TNBC), or laterality (right vs. left). The use of H-WBI increased from 28%±10% to 76%±6% in patients with pure DCIS (otherwise guideline endorsed), from 33%±12% to 61%±9% in patients with a SEP >25 cm (otherwise guideline endorsed), and from 6%±11% to 40%±21% in patients who received systemic chemotherapy (otherwise guideline endorsed). However, the increase in H-WBI use was more modest for patients younger than 50 years but otherwise guideline endorsed (20%±35% to 38%±34%). In this large, multi-center cohort, the use of H-WBI has increased over the last 5 years in all patient subsets, albeit with less frequency in those who did not meet all guideline criteria, particularly in patients who received chemotherapy and those <50 years of age. As updated guidelines for H-WBI are imminent, further examination of uptake in the use of H-WBI as well as the clinical outcomes and toxicities in these subgroups is warranted.

Lymph node ratio is inferior to pN-stage in predicting outcome in colon cancer patients with high numbers of analyzed lymph nodes

BackgroundThe lymph node ratio (LNR), i.e. the number of positive lymph nodes (LN) divided by the total number of analyzed LN, has been described as a strong outcome predictor in node-positive colon cancer patients. However, most published analyses are constrained by relatively low numbers of analyzed LN. Therefore, the objective of the present study was to evaluate the prognostic impact of LNR in colon cancer patients with high numbers of analyzed LN.MethodsOne hundred sixty-six colon cancer patients underwent open colon resection. All node-positive patients were analyzed for this study. The number of analyzed LN, of positive LN, the disease-free (DFS) and overall survival (OS) time were prospectively recorded. Patients were dichotomously allocated to a high or a low LNR-group, respectively, with the median LNR (0.125) as a cut-off value. Median follow-up was 34.3 months.ResultsFifty-eight patients (34.9%) were node-positive. The median number of analyzed LN was 23 (range 8–54). DFS and OS were significantly shorter in pN2 vs pN1 patients (p < 0.001, and p = 0.001, respectively), and in LNR high vs low patients (p = 0.032, and p = 0.034, respectively). pN2 (vs pN1) disease showed hazard ratios (HR) of 6.2 (p < 0.001), and 6.8 (p < 0.005; for DFS and OS, respectively), while LNR high (vs low) showed HR of 3.0 (p =0.041), and 4.5 (p = 0.054).ConclusionsLNR is a reasonable outcome predictor in node-positive colon cancer patients. However, LNR is inferior to pN-stage in predicting survival in patients with high number of harvested lymph nodes.

Pathological risk factors stratification in pN3b oral cavity squamous cell carcinoma: Focus on the number of positive nodes and extranodal extension

ObjectiveAccording to the AJCC 2017 Staging Manual, oral cavity squamous cell carcinoma (OCSCC) with pN2 disease (based on the AJCC 2010 criteria) and extra-nodal extension (ENE) should be classified as pN3b. We performed a detailed outcome analyses in this patient subgroup. Material and methodsWe retrospectively reviewed the clinical records of consecutive OCSCC patients who underwent radical surgery between 1996 and 2017. Patients with pN3b disease (n = 365) were divided into a pN+ ≥8/ENE ≥5 subgroup (defined by the presence of pN+ ≥8 nodes or ENE ≥5 nodes, n = 77) and a pN+ ≤7/ENE ≤4 subgroup (defined by the presence of pN+ ≤7 nodes and ENE ≤4 nodes, n = 288). Patients with pN0/pN1/pN2 (n = 1192/179/197) disease were included for comparison purposes. ResultsPatients in the pN+ ≥8/ENE ≥5 subgroup had less favorable 5-year outcomes than those in the pN+ ≤7/ENE ≤4/pN2/pN1/pN0 groups (local control, 64%/79%/86%/83%/88%, p < 0.001; neck control, 55%/75%/80%/86%/93%, p < 0.001; distant metastases, 67%/28%/20%/12%/3%, p < 0.001; disease-free survival, 21%/51%/64%/72%/82%, p < 0.001; disease-specific survival, 25%/55%/71%/82%/92%, p < 0.001; overall survival, 19%/40%/54%/64%/82%, p < 0.001; respectively). Among patients with pN3b disease, multivariable analysis identified the pN+ ≥8/ENE ≥5 subgroup, lower neck (level IV/V) metastases, and depth of invasion ≥25 mm as independent adverse prognostic factors for 5-year distant metastases and survival rates. ConclusionsPatients in the pN+ ≥8/ENE ≥5 subgroup have an unfavorable prognosis and their classification as pN3b is advisable. In contrast, patients in the pN+ ≤7/ENE ≤4 subgroup should be classified as pN3a.

A negative multiparametric magnetic resonance imaging finding does not guarantee the absence of significant cancer among biopsy-proven prostate cancer patients: a real-life clinical experience.

We analyzed the data of consecutive patients who had preoperative multiparametric magnetic resonance imaging (mpMRI) and underwent radical prostatectomy (RP) to evaluate the actual performance of mpMRI among biopsy-proven prostate cancer (PCa) patients in predicting favorable pathology in the real-life clinical setting. Among a total 730 biopsy-proven PCa patients underwent RP, the preoperative mpMRIs of 534 patients were positive, demonstrating one or more PI-RADs V2 grade ≥ 2 lesion(s). Other 196 mpMRIs were classified as negative, without any suspicious lesion. Pathology was classified to be unfavorable when showing Gleason score (GS) 4/5 or pT3/N1 features. Significant cancer was defined as non-organ-confined, GS 4/5, or cancer volume of ≥ 0.5mL. Among a total 196 negative preoperative mpMRI patients, final RP pathology showed that 20 (10.2%) had pT3 disease and 2 (1.0%) had pN1 disease. Regarding the pathologic Gleason score, 117 (59.7%) had GS 3 + 4 and 44 (22.4%) had GS ≥ 4 + 3. The rate of a favorable PCa and an insignificant cancer was as low as 14.3% and 10.2%. Even among only the 101 D'Amico low-risk patients with negative MRI, the rates of a favorable pathology and an insignificant cancer were only 18.2% and 12.7%. The sensitivity, specificity, positive, and negative predictive value of mpMRI to predict a significant cancer were 74.3%, 45.5%, 95.5%, and 10.2%, respectively. In the real-life clinical setting, mpMRI demonstrated limited performance in the prediction of favorable and insignificant prostate cancer as a negative mpMRI could not guarantee the absence of unfavorable pathology among PCa patients.

Long term survival after hepatectomy for intrahepatic cholangiocarcinoma: a tool for preoperative prediction

Introduction: Hepatectomy stands as the only curative treatment for intrahepatic cholangiocarcinoma (IHCC). Still, long term survival is rarely achieved as most patients experience recurrence and die shortly after resection. This study aimed to develop a predictive model of long term survival. Methods: Among patients who underwent curative-intent hepatectomy for IHCC from a multicenter database (n=249), patients who remained disease free 5 years after resection (DFS5+) were compared to those who recurred and died of disease within 5 years (DFS5-) for developing a predictive model of DFS5+. This model was then applied in a single center cohort (n=189) for external validation. Results: Among the training cohort, 196 patients (78.7%) were DFS5- and 53 (21.3%) were DFS5+. Upon multivariable analysis, tumor size (OR=1.16, p=0.014), multifocal disease (OR=3.1, p=0.006), pN1 status (OR=8.2, p=0.007) and R1 status (OR=2.32 p=0.026) were independently associated with SSR5+. Among DFS5+ patients, two patients (3%) had pN1 disease. Using these variables, a predictive model was developed and showed high predictive performances (C-index = 0.84) in the development cohort. Predictive performances are currently being assessed in the validation cohort. Conclusion: Actual DFS5+ rate is lower as compared to actuarial rates classically reported in large series. Although tumor size, multifocality and planned R status could be preoperatively assessed using imaging, knowing pN status through portal lymphadenectomy would help predicting long term survival before hepatectomy. The present model developed could help decision making for upfront surgery or neoadjuvant strategy according to 5-year DFS probability.

Is age alone a predictor for receipt of adjuvant chemotherapy in patients with resected gallbladder cancer?

Introduction: Role of adjuvant therapy for resected gallbladder cancer remains unclear. There are no randomized trials to guide clinicians in this regard and retrospective studies remain split on efficacy of adjuvant treatment options. Method: The National Cancer Data Base (NCDB) was queried for patients with non-metastatic, resected gallbladder cancer diagnosed between 2004 and 2013. Baseline characteristics were compared using chi-square test and factors associated with adjuvant chemotherapy administration were analyzed using multivariate logistic regression model. Results: A total of 4486 patients were identified. Majority of the patients were >65 years of age (65.2%). In the full cohort analysis, patients who received adjuvant chemotherapy were more likely to be: younger, of Hispanic ethnicity, with no comorbidities, diagnosed from 2010-2013, with poorly differentiated histology, pT3, pN1, undergoing radical resection and receiving adjuvant radiation (p < 0.05). Subgroup analysis of patients receiving chemotherapy was done which demonstrated higher odds of single-agent chemotherapy administration among patients who: were elderly, diagnosed from 2004–2009, had well differentiated histology, pT1 & pN0 disease, belonged to the lowest income quartile and received adjuvant radiation (p < 0.05). [Table 1] Conclusions: In patients with resected gallbladder cancer, receipt of adjuvant chemotherapy is affected by several patient- and disease-specific factors and not just age alone.